Dopamine fails to stimulate protein kinase C activity in renal proximal tubules of spontaneously hypertensive rats

Clin Exp Hypertens. 1995 Jul;17(5):837-45. doi: 10.3109/10641969509033638.


We have previously reported that dopamine-1 receptor-mediated activation of phospholipase C is diminished in renal cortical slices of spontaneously hypertensive rats. The present study was carried out to examine the effect of dopamine on protein kinase C (PKC), which is one of the enzymes involved in the signal-transduction pathway leading to dopamine-induced inhibition of Na+/K(+)-ATPase in the renal proximal tubule. Renal proximal tubule suspensions were obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats of 10-12 weeks old. The tubules were incubated with dopamine in the presence or absence of DA-1 receptor antagonist SCH 23390. The PKC activity was measured by using a specific fluorescent peptide substrate (sequence, PKSRTLSVAAK). We found that dopamine produced a concentration-dependent increase in protein kinase C activity in the WKY rats, however, it failed to stimulate PKC activity in the SHR. Peak stimulation of 3.828 +/- 0.35 (ng/micrograms) protein in the WKY rats was observed at dopamine concentration of 1 microM, which was blocked in a concentration-dependent manner by SCH 23390 (0.25 microM). These results provide evidence that dopamine directly stimulates PKC activity via activation of DA-1 receptors in WKY rats. Furthermore, we discovered that dopamine fails to stimulate PKC activity in the SHR. This phenomenon may be responsible for the failure of dopamine to inhibit Na+/K(+)-ATPase activity in the hypertensive animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Benzazepines / pharmacology
  • Dopamine / pharmacology*
  • Enzyme Activation / drug effects
  • Fluorescent Dyes / chemistry
  • Hypertension / enzymology*
  • In Vitro Techniques
  • Kidney Tubules, Proximal / drug effects*
  • Kidney Tubules, Proximal / enzymology*
  • Male
  • Molecular Sequence Data
  • Oligopeptides / chemistry
  • Protein Kinase C / metabolism*
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Substrate Specificity


  • Benzazepines
  • Fluorescent Dyes
  • Oligopeptides
  • Protein Kinase C
  • Sodium-Potassium-Exchanging ATPase
  • Dopamine